NM_021930.6:c.2362C>A

Variant names:

• chr7-105567294-C-A
• rs1060503046
• NM_021930.6:c.2362C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021930.6(RINT1):​c.2362C>A​(p.Pro788Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P788L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RINT1 NM_021930.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.15
• Publications: 0 publications found

Genes affected

RINT1 (HGNC:21876): (RAD50 interactor 1) This gene encodes a protein first identified for its ability to interact with the RAD50 double strand break repair protein, with the resulting interaction implicated in the regulation of cell cycle progression and telomere length. The encoded protein may also play a role in trafficking of cellular cargo from the endosome to the trans-Golgi network. Mutations in this gene may be associated with breast cancer in human patients. [provided by RefSeq, Oct 2016]

EFCAB10 (HGNC:34531): (EF-hand calcium binding domain 10) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021930.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RINT1	NM_021930.6	MANE Select	c.2362C>A	p.Pro788Thr	missense	Exon 15 of 15	NP_068749.3
	EFCAB10	NM_001355526.2	MANE Select	c.383+173G>T		intron	N/A	NP_001342455.1	A6NFE3
	RINT1	NM_001346599.2		c.2128C>A	p.Pro710Thr	missense	Exon 15 of 15	NP_001333528.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RINT1	ENST00000257700.7	TSL:1 MANE Select	c.2362C>A	p.Pro788Thr	missense	Exon 15 of 15	ENSP00000257700.2	Q6NUQ1
	EFCAB10	ENST00000486180.5	TSL:1	c.*160G>T		3_prime_UTR	Exon 4 of 4	ENSP00000417484.1	J3KR48
	EFCAB10	ENST00000480514.6	TSL:1 MANE Select	c.383+173G>T		intron	N/A	ENSP00000418678.1	A6NFE3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.51	D
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.2
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.30
Sift	Benign	0.091	T
Sift4G	Uncertain	0.024	D
Polyphen		1.0	D
Vest4		0.48
MutPred		0.48		Gain of MoRF binding (P = 0.0166)
MVP		0.65
MPC		0.75
ClinPred		0.99	D
GERP RS		6.0
Varity_R		0.35
gMVP		0.45
Mutation Taster		=37/63	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1060503046; hg19: chr7-105207741;